Ubiquitin C-Terminal Hydrolase L1 in Tumorigenesis

Figure 1

Molecular functions of ubiquitin c-terminal hydrolase L1. (1) UCH-L1 can hydrolyze ubiquitin pro-proteins to generate monomeric ubiquitin (Ub) [29]. (2) UCH-L1 may also facilitate Ub recycling by processing Ub chains. (3) UCH-L1 has been reported to stabilize monomeric Ub by binding to Ub and preventing its degradation by the lysosome [4]. Collectively, these functions (1, 2, and 3) give UCH-L1 control over the availability of free Ub and, therefore, the potential to influence many ubiquitination-dependent cellular processes, including proteasomal degradation, DNA damage repair, trafficking, cell signaling, endocytosis, and lysosomal degradation. (4) Dimerized UCH-L1 may possess ATP-independent E3 ligase activity that facilitates K63-linked polyubiquitination [5], although it is currently unclear whether this putative E3 ligase activity directly regulates ubiquitination of protein substrates in vivo. (5) Altered expression of UCH-L1 may cause changes to the free Ub pool, resulting in abnormal K48-linked polyubiquitination and proteasomal degradation. (6) Changes in the free Ub pool may also affect mono- and K63-linked polyubiquitination, leading to altered nonproteasomal functions and tumorigenesis.